title: Dietary linoleic acid elevates the endocannabinoids 2-AG and anandamide and promotes weight gain in mice fed a low fat diet.
abstract: Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P. O. Box 2029, Nordnes, 5817, Bergen, Norway.
authors.forename: Anita Røyneberg
authors.initials: AR
authors.lastname: Alvheim
authors.forename: Bente E
authors.initials: BE
authors.lastname: Torstensen
authors.forename: Yu Hong
authors.initials: YH
authors.lastname: Lin
authors.forename: Haldis Haukås
authors.initials: HH
authors.lastname: Lillefosse
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Lock
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.forename: Livar
authors.initials: L
authors.lastname: Frøyland
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hibbeln
authors.forename: Marian Kjellevold
authors.initials: MK
authors.lastname: Malde
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004032:Diet; D018752:Diet, Fat-Restricted; D063388:Endocannabinoids / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005989:Glycerides / Q000378:metabolism; D020738:Leptin / Q000097:blood; D019787:Linoleic Acid / Q000008:administration & dosage / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D012307:Risk Factors; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005227:Fatty Acids; D005989:Glycerides; D020738:Leptin; D010743:Phospholipids; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; D019787:Linoleic Acid; C078814:anandamide